Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:B0FTZ7 (catenin)
 18,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuroendocrine tumours (NETs) of the lung represent a wide spectrum of phenotypically distinct entities, with differences in tumour progression and aggressiveness. The redistribution and/or the loss of various cell adhesion molecules, such as the E-cadherin-catenin complex, play a predominant role in carcinogenesis and in tumour invasion. Moreover, mutations in exon 3 of the beta-catenin gene, the adenomatous polyposis coli (APC) gene or the E-cadherin genes were previously found to result in intracytoplasmic and/or nuclear beta-catenin protein accumulation, activating nuclear transcription of target genes involved in tumour progression. In the present study, the distribution of the components of this E-cadherin-catenin complex has been investigated by immunohistochemistry and an attempt has been made to correlate the abnormal expression pattern with the eventual detection of mutations in the corresponding genes. This study included 27 primary NETs of the lung, with nine typical carcinoids (TCs), three atypical carcinoids (ACs), and 15 large cell neuroendocrine carcinomas (LCNECs). The E-cadherin-catenin complex remained expressed in most of these lung tumours, but with a cytoplasmic and/or nuclear redistribution of beta-catenin, E-cadherin, and alpha-catenin; abnormal positive immunoreactivity was observed in 24 (88.9%), in 21 (80.8%), and in 20 (76.9%) NETs, respectively. In the great majority of cases, there was a good correlation between the expression of these three proteins, but no significant association with histological classification or TNM stage. Thus, E-cadherin-complex redistribution cannot be considered a prognostic marker in NET of the lung. Of particular interest was the frequent focal beta-catenin nuclear immunostaining (55.5% in total), which was also unrelated to histological type or TNM stage. However, this study failed to detect any mutation in exon 3 of the beta-catenin gene, in the APC gene or in the E-cadherin gene. These data suggest another mechanism of regulation of beta-catenin in these tumours.
 ...
PMID:Expression of the E-cadherin-catenin complex in lung neuroendocrine tumours. 1132 37

Dysfunction of E-cadherin and catenin has been linked to invasiveness and differentiation of tumors. This study aimed to characterize the expression of cadherins and catenins in early gastric carcinoma and their relationship to clinicopathologic characteristics and Helicobacter pylori infection. E-cadherin and alpha-, beta- and gamma-catenins were strongly expressed in normal epithelium but abnormal immunoreactivity of at least one of these four proteins was noted in 48 (90.6%) of 53 early gastric carcinomas. Only 5 cases with intestinal-type tumors had intact expression of E-cadherin and alpha-, beta-, and gamma-catenins. Abnormal immunoreactivity in the tumor tissue was observed in 18 patients (34.0%) for E-cadherin, in 35 (66.0%) for alpha-catenin, in 20 (37.7%) for beta-catenin, and in 37 (69.8%) for gamma-catenin. In diffuse-type tumors, abnormal expression of E-cadherin (60.9 vs. 13.3%, p < 0.0005), alpha-catenin (82.6 vs. 53.3%, p < 0.05) and gamma-catenin (91.3 vs. 53.3%, p < 0.005) was more frequent than in the intestinal type. Ten tumors with lymph node metastasis showed a relatively higher frequency of abnormal expression of E-cadherin (70 vs. 25.6%, p < 0.05) but a lower frequency of abnormal expression of beta-catenin (10 vs. 44.1%, p = 0.07) than those without metastasis. No significant association was found between cadherin/catenin expression and the depth of invasion or the H. pylori status. It was concluded that abnormal expression of E-cadherin and the catenin-mediated cell-cell adhesion system occurs frequently in early gastric carcinogenesis and may play an important role in the genesis of histologic differentiation and in the mode of metastasis of early gastric carcinomas.
 ...
PMID:Immunohistochemical evaluation of cadherin and catenin expression in early gastric carcinomas: correlation with clinicopathologic characteristics and Helicobacter pylori infection. 1140 2

Similar to findings in colorectal cancers, it has been suggested that disruption of the adenomatous polyposis coli (APC)/beta-catenin pathway may be involved in breast carcinogenesis. However, somatic mutations of APC and beta- catenin are infrequently reported in breast cancers, in contrast to findings in colorectal cancers. To further explore the role of the APC/beta-catenin pathway in breast carcinogenesis, we investigated the status of APC gene promoter methylation in primary breast cancers and in their non-cancerous breast tissue counterparts, as well as mutations of the APC and beta- catenin genes. Hypermethylation of the APC promoter CpG island was detected in 18 of 50 (36%) primary breast cancers and in none of 21 non-cancerous breast tissue samples, although no mutations of the APC and beta- catenin were found. No significant associations between APC promoter hypermethylation and patient age, lymph node metastasis, oestrogen and progesterone receptor status, size, stage or histological type of tumour were observed. These results indicate that APC promoter CpG island hypermethylation is a cancer-specific change and may be a more common mechanism of inactivation of this tumour suppressor gene in primary breast cancers than previously suspected.
 ...
PMID:Adenomatous polyposis coli (APC) gene promoter hypermethylation in primary breast cancers. 1143 4

The cadherin-catenin system mediates Ca(2+)-dependent cell-cell adhesion, and genetic alterations in these molecules play a significant role in multistage carcinogenesis. Mutations in the beta-catenin gene, mostly affecting exon 3, have been detected in malignant cell lines and in primary tumors. Immunohistochemical abnormalities in alpha-, beta-, and gamma-catenin have been reported in malignant and benign tumors, and nuclear localization of beta-catenin has been associated with mutations in exon 3 of this gene. Mutational analysis of exon 3 of the beta-catenin gene was undertaken by polymerase chain reaction (PCR) and sequencing using genomic DNA extracted from frozen tissues, including 4 normal pituitaries, 22 pituitary adenomas, and one pituitary carcinoma. Frozen sections from these cases were used for immunohistochemical detection of beta-catenin. We also analyzed immunohistochemical expression of alpha-, beta-, and gamma-catenin by paraffin sections from 154 pituitary tumors, including 148 adenomas and 6 carcinomas. Genomic DNA was extracted from paraffin sections of 2 gonadotroph tumors showing nuclear staining for beta-catenin and was used for PCR and sequencing of exon 3 of the beta-catenin gene. No mutations in exon 3 of the beta-catenin gene were found in any of the 23 cases analyzed by PCR and sequencing. In addition, the 2 cases studied by paraffin section immunohistochemistry, with nuclear staining for beta-catenin, were negative for mutations in this exon. Normal pituitary expressed all three catenin proteins. Immunostaining usually showed a membranous pattern of reactivity and was generally stronger in normal pituitary than in the adjacent adenomas. Stains for alpha-catenin were positive in fewer tumors than for beta-catenin. The lowest frequency immunopositive tumors and the weakest immunostaining was for gamma-catenin. All medically treated prolactinomas were negative for gamma-catenin, whereas treated growth hormone adenomas were less often positive for both alpha- and gamma-catenin than for untreated tumors. The percentage of positive cases for beta-catenin was the same in these two groups. Most pituitary carcinomas were negative for both alpha- and gamma-catenin but were beta-catenin positive. These results indicate that (i) mutations in exon 3 of the beta-catenin gene are uncommon in pituitary tumors, and (ii) expression of alpha-, beta-, and gamma-catenin is decreased in pituitary adenomas compared to normal pituitary tissues.
 ...
PMID:Analysis of beta-catenin mutations and alpha-, beta-, and gamma-catenin expression in normal and neoplastic human pituitary tissues. 1157 78

Transforming growth factor beta1 (TGF-beta1) acts as a tumor suppressor at early stages of carcinogenesis, however, it has also been suggested to promote tumor progression at late stages. To determine at which stage and by what mechanisms this functional switch occurs, we have generated gene-switch-TGF-beta1 mice in which TGF-beta1 transgene expression can be induced in skin tumors at specific stages. These mice were exposed to a chemical carcinogenesis protocol, which allows tumorigenesis to develop in progressive stages from benign papillomas to malignant carcinomas. Remarkably, TGF-beta1 transgene induction in papillomas rapidly induced metastasis. This function is in sharp contrast to its tumor suppressive effect when TGF-beta1 transgene expression was induced early in the protocol. Transgenic papillomas exhibited down-regulation of TGF-beta receptors and their signal transducer, the Smads, and loss of the invasion suppressor E-cadherin/catenin complex in the cell membrane. These molecules were lost only in malignant carcinomas in control mice at a much later stage. Furthermore, transgenic papillomas exhibited elevated expression of matrix metalloproteinases and increased angiogenesis. Our study suggests that TGF-beta1 overexpression may directly induce tumor metastasis by initiating events necessary for invasion. Down-regulation of TGF-beta signaling components in tumor epithelia selectively abolishes growth inhibition, thus, switching the role of TGF-beta1 to a metastasis promoter.
 ...
PMID:Inducible expression of transforming growth factor beta1 in papillomas causes rapid metastasis. 1160 77

Indomethacin-induced G(1) arrest and apoptosis of human colorectal cancer (CRC) cells is associated with a dose-dependent decrease in beta-catenin protein levels. Beta-catenin plays a pivotal role in the WNT signalling pathway and its expression is frequently dysregulated at early stages of colorectal carcinogenesis. The objective of this study was to investigate the effect of indomethacin on catenin expression and downstream WNT signalling events in human CRC cells. Beta-catenin, gamma-catenin and T-cell factor (TCF) target gene (cyclin D1, c-MYC and PPARdelta) expression was studied following indomethacin treatment of SW480 and HCT116 cells. Cyclin D1 was used as a model TCF target gene for analysis of beta-catenin-TCF-4 DNA binding and trans-activation. Indomethacin treatment was associated with a specific decrease in beta-catenin (but not gamma-catenin) expression. Resulting TCF target gene expression was gene specific (cyclin D1, decreased; c-MYC, increased; PPARdelta, no significant change). Cyclin D1 promoter analysis revealed that indomethacin disrupted formation of a beta-catenin-TCF-4-DNA complex. Indomethacin-induced G(1) arrest and apoptosis is associated with specific beta-catenin down-regulation in human CRC cells in vitro. Differential expression of TCF target genes following indomethacin treatment implies complex effects on multiple genes which play an important role in colorectal carcinogenesis.
Carcinogenesis 2002 Jan
PMID:Indomethacin induces differential expression of beta-catenin, gamma-catenin and T-cell factor target genes in human colorectal cancer cells. 1175 31

Hepatocellular carcinoma (HCC) accounts for 80-90% of liver cancers and is one of the most frequent carcinomas throughout the world. The disease is more prevalent in parts of Africa and Asia than in North and South America and Europe, with a strong etiological association with viral hepatitis, hemochromatosis, known liver (hepatic) carcinogens, and toxins (mycotoxins). Clinical and molecular medical analyses have yielded a considerable amount of information about liver carcinogenesis. Many genes undergo somatic aberrations, with a tendency to cluster at genes involved in cell cycle regulation, in the p53 and Wnt/catenin pathways of signal transduction and cellular adhesion, and in the TGF-beta/IGF axis. Since HCC may arise both in liver cirrhosis and in noncirrhotic liver, one may speculate that different hepatocarcinogenetic pathways exist. Recent results of high-output gene analysis using cDNA microarrays support the idea of different genetic alterations in HCC with or without cirrhosis.
 ...
PMID:Genes involved in hepatocellular carcinoma: deregulation in cell cycling and apoptosis. 1195 13

E-cadherin and its associated cytoplasmic proteins including alpha-, beta-, and gamma-catenin play a pivotal role in the maintenance of normal tissue architecture and the suppression of cancer invasion. The purpose of this study was to evaluate the expression of E-cadherin and alpha-, beta-, and gamma-catenin in a larger sample of early gastric cancer, and to examine the relation between these expressions and various clinicopathologic variables. The expression of E-cadherin and alpha-, beta-, and gamma-catenin was investigated using immunohistochemical technique with formalin-fixed, paraffin-embedded tissue specimens obtained from 108 patients who underwent surgery for early gastric cancer. In the gastric mucosa of noncancerous areas, epithelial cells showed equally strong membranous expression of E-cadherin and alpha-, beta-, and gamma-catenin proteins at the cell-cell boundaries. Reduced expression of E-cadherin and alpha-, beta-, and gamma-catenin was demonstrated in 43.5%, 39.8%, 42.6%, and 50% of cancer tissues, respectively. Whereas 34 tumors (31.5%) displayed preserved expression of all four E-cadherin-catenin complex components, 21 tumors (19.4%) displayed reduced expression of all components of this complex. Reduced expression of E-cadherin and alpha- and gamma-catenin occurred more frequently in diffuse than in intestinal types of cancer, and decreased expression of E-cadherin and alpha-, beta-, and gamma-catenin correlated with poor differentiation. The expression of E-cadherin and beta- and gamma-catenin did not correlate with the patient's age, gender, tumor size, location, macroscopic type, depth of invasion, or lymph node metastasis. Only reduced expression of alpha-catenin correlated with lymph node metastasis. Reduced expression of all four E-cadherin-catenin complex components correlated with poorly differentiated and diffuse-type cancers, but not with the patient's age, gender, tumor size, location, macroscopic type, depth of invasion, or lymph node metastasis. These results suggest that dysfunction of the E-cadherin-catenin complex occurs in an early stage of carcinogenesis, playing a crucial role in disruption of tissue architecture and loss of differentiation in early gastric cancer.
 ...
PMID:Expression of e-cadherin and catenins in early gastric cancer. 1208 Feb 24

Changes in the expression of microfilament-associated proteins, such as tropomyosins (TMs), are commonly found in malignantly transformed cells. Previous work from this laboratory has shown that tropomyosin-1 (TM1) expression is consistently abolished in human breast carcinoma cell lines, suggesting that the loss of TM1 could be a common biochemical event in the transformation of mammary epithelium. To investigate whether changes in TM1 expression are causally linked to mammary carcinogenesis, we have tested the hypothesis that TM1 is a tumor suppressor of breast cancer. MCF-7 cells, which lack TM1, were utilized as a model of human breast cancer and transduced to reexpress TM1 protein. Restoration of TM1 expression in MCF-7 cells (MCF-7/T cells) resulted in a slower growth rate, but cells remained sensitive to growth control by estrogen. TM1 expression in MCF-7 cells resulted in the emergence of TM-containing microfilaments. More significantly, MCF-7/T cells failed to grow under anchorage-independent conditions. TM1 reexpression alters the interaction of the E-cadherin-catenin complex with the cytoskeleton, indicating that TM1-induced cytoskeleton could play a significant role in suppression of the malignant phenotype. Taken together with our previous work on transformed murine fibroblasts, the results presented in this communication indicate that in nonmuscle cells TM1 functions as a suppressor of transformation.
 ...
PMID:Suppression of the transformed phenotype of breast cancer by tropomyosin-1. 1221 12

Although dehydroepiandrosterone (DHEA) is recognized as one of the major adrenal androgens, its precise physiological role in the human endocrine system remains to be elucidated. In particular, the effect of DHEA on carcinogenesis has not been fully characterized. We undertook this study to determine whether DHEA has a chemopreventative effect on the precursors of colon cancer in a murine model of azoxymethane (AOM)-induced aberrant crypt foci (ACF). The number of ACF was significantly decreased in mice treated with 0.4% (p < 0.001) and 0.8% DHEA (p < 0.001), but there were no significant differences between DHEA-treated and control mice in terms of the ACF size, 3-catenin expression or level of dysplasia. This is the first study of colon cancer carcinogenesis demonstrating that DHEA treatment can decrease the number of ACF without apparently modifying their malignant potential. These data strongly suggest that DHEA might be a potential chemopreventative agent against human colon cancer.
 ...
PMID:Chemoprevention of precursors to colon cancer by dehydroepiandrosterone (DHEA). 1226 89


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>